Human fibrosarcoma cell lines have been found to be transformed in vitro and tumorigenic when injected into immunosuppressed animals. We have hybridized one human fibrosarcoma cell line (HT-1080) with mouse peritoneal macrophages and with contact inhibited mouse fibroblasts. Three different types of somatic cell hybrids were obtained: a) those which have lost mouse chromosomes; b) those which have retained the entire complement of mouse and human chromosomes; and c) those which have lost human chromosomes. These different hybrid cells were found to be tumorigenic in nude mice. We propose: a) To identify the human chromosome responsible for the expression of malignancy in the HT-1080 human fibrosarcoma cell line; b) to characterize the tumor antigens expressed in the cell surface of the Ht-1080 human fibrosarcoma cells; c) to select for temperature sensitive (ts) mutants for transformation of HT-1080 human fibrosarcoma cells; d) to hybridize normal mouse cells with ts mutants of HT-1080 cells in order to determine if the temperature sensitive mutations affect the human chromosome responsible for transformation; and e) to identify the human chromosome responsible for the expression of malignancy in additional human fibrosarcoma cell lines.